We have successfully cloned and structurally characterized three cDNA clones of the mouse mu, alpha and gamma 2b constant regions and have also prepared partial EcoRI derived genomic DNA libraries of three myelomas expressing the C mu, C alpha and C gamma 2b genes respectively and the Balb/c/J germ line. Multiple representative clones of the C mu, C alpha and C gamma 2b genes have thus far been isolated and structually characterized. Restriction mapping and southern blot hybridizations on total genomic DNAs and our purified CH clones have disclosed a most interesting phenomena to us. Variations in the flanking DNA sequence organization of the CH genes appears not only to occur in plasmacytomas but in different in bred mouse strain germ lines as well. Mouse strain variations appear to be due to variable sized DNA deletions occurring 5' proximal to different CH genes. These labile sequences may play an important role in the CH gene switching mechanism during the ontogeny of B cell differentiation by serving as receiving sites for DNA recombinations and translocations. We propose to extend our observations by precisely defining the nature and similarities of these deletable sequences. In addition, the role of these regions as potential recombination sites in plasmacytomas, which are known to have switched their CH genes in tissue culture or in hybridoma cell lines, which appear to express heavy chains with identical variable regions linked to different constant regions, will be investigated.